Effects of naringenin on ocular blood flow and choroidal neovascularization in experimental animals

AIM: To investigate the effects of naringenin on laser- induced experimental choroidal neovascularization (CNV) in rat models, ocular blood flow and retinal function recovery after ischemic insults in rat eyes. METHODS: Male Brown Norway rats were treated to break the Bruch's membrane. Naringenin 10g/L (20mg/kg) was given once per day through intraperitoneal injection for 4 weeks after laser treatment. The development of CNV was determined by fluorescein angiography (FA) performed on week 2 and 4. The colored microsphere technique and electroretinography method were used for the study of ocular blood flow and retinal function recovery, respectively. RESULTS: The choroidal blood flow in elevated intraocular pressure (IOP) rabbit eyes was significantly increased by 10g/L naringenin solution as compared to control group (P < 0.05). The retinal function recovery after ischemic insults in rat eyes indicated significant increase of b-wave recovery in treated group, as compared to control group (P <0.05). The intensity of fluorescein leakage from the photocoagulated lesions significantly decreased in treated group, compared to the control group (75.8%-95.0%, P <0.01). CONCLUSION: Naringenin could prevent the development of CNV on laser-induced experimental rat models, increase the choroidal blood flow in elevated IOP rabbit eyes and be beneficial on retinal function recovery in ischemic rat eyes.     

Effect of topical epinephrine and timolol on ocular and optic nerve blood flow in phakic and aphakic rabbit eyes

The effects of 4% epinephrine bitartrate and 0.5% timolol on ocular and optic nerve blood flow were studied in phakic and aphakic rabbit eyes using a radioactive microsphere (85Sr) technique. Either epinephrine or timolol was given topically as eight drops in the hour immediately preceding blood flow measurements (one drop every 7.5 minutes). Epinephrine decreased anterior uveal blood flow in both phakic and aphakic eyes, whereas timolol exhibited no effect. Retinal and choroidal blood flow were not affected by either timolol or epinephrine in phakic eyes. In aphakic eyes, epinephrine increased choroidal blood flow without altering retinal blood flow, whereas timolol increased both retinal and choroidal blood flow. Optic nerve blood flow was increased in epinephrine treated phakic and aphakic eyes and also in timolol treated aphakic eyes.     

Effects of brinzolamide on aqueous humor dynamics in monkeys and rabbits.

This study examines the mechanisms by which brinzolamide reduces intraocular pressure (IOP) in healthy rabbits and in monkeys with unilateral ocular hypertension. Intraocular pressures were measured by pneumatonometry and aqueous flow was determined by fluorophotometry before and after three twice-daily drops of 1% brinzolamide to both eyes per monkey and after similar treatment to one eye per rabbit. In monkeys, outflow facility was determined by fluorophotometry and uveoscleral outflow was calculated. In rabbits, outflow facility was determined by two-level constant pressure infusion and uveoscleral outflow was measured by an intracameral tracer technique. Compared with contralateral vehicle-treated rabbit eyes, IOP was reduced in brinzolamide-treated eyes by 2.5 +/- 1.9 mmHg (mean +/- standard deviation; p =.006) at four hours after the second dose. Aqueous flow was reduced by 0.50 +/- 0.65 microl/min (p =.02). This effect was found in rabbits previously treated with brinzolamide but not in naive rabbits. Treated hypertensive eyes of monkeys had a reduction in IOP of 7.3 +/- 8.8 mmHg (p = 0.01) and aqueous flow of 0.69 +/- 1.10 microL/min (p = 0.05) when compared with baseline. Brinzolamide did not affect outflow facility or uveoscleral outflow in either rabbits or monkeys. It is concluded that, in normotensive eyes of rabbits and hypertensive eyes of monkeys, brinzolamide reduces IOP by reducing aqueous flow and not by affecting aqueous humor drainage.     

Impact of simulated light scatter on scanning laser Doppler flowmetry

AIM: To determine the impact of simulated light scatter on scanning laser Doppler flowmetry (SLDF) assessment of retinal capillary blood flow and retinal image quality. METHODS: One eye of 10 normal subjects (mean (SD) age 24 (1.7) years, range 22-27) was randomly selected. Varying concentrations of polystyrene microspheres were suspended in optically clear cells to simulate light scatter. The microsphere concentrations used were 0.05%, 0.03%, 0.02%, 0.01%, and a cell containing only water. LogMAR visual acuity and contrast sensitivity were measured both with and without cells. Optimal focus and alignment was established by acquiring three SLDF images each of the optic nerve head (ONH) and of the macula using the Heidelberg retina flowmeter (HRF) with no cell in place. SLDF images were subsequently acquired with each of the light scatter cells mounted in front of the HRF. The group mean retinal capillary blood flow was compared using repeated measures analysis of variance (reANOVA) as a function of microsphere concentration. RESULTS: Retinal capillary blood flow increased significantly in the ONH, nasal macula, fovea, and temporal macula with increasing microsphere concentration (p<0.0001). Using Dunnett's post hoc test, retinal capillary blood flow was found to be significantly increased relative to the no cell condition for the 0.03% and 0.05% cell concentrations. CONCLUSIONS: Simulated light scatter produces an artifactual increase in retinal capillary blood flow. The impact of cataract on SLDF measurements has yet to be determined.     

ZX-5及其光学异构体对兔眼血流和大鼠视网膜功能恢复的影响

目的:研究ZX-5对缺血后视网膜功能的恢复作用,并比较其光学异构体(R,R)-ZX-5和(S,S)-ZX-5对脉络膜血流及缺血后视网膜功能恢复的影响。方法:用彩色微球技术研究兔高眼压下(40mmHg)脉络膜血流的变化。用视网膜电生理仪测量b波,评价大鼠缺血后视网膜功能的恢复情况。结果:10g/L(R,R)-ZX-5滴眼液50μL能在不同时间点提高脉络膜血流(P<0.05),而(S,S)-ZX-5在相同条件下对提高脉络膜血流没有影响。ZX-5和(R,R)-ZX-5在不同时间点对视网膜缺血后功能恢复作用明显(P<0.05),(R,R)-ZX-5的作用优于ZX-5;而(S,S)-ZX-5对缺血后视网膜功能的恢复作用不明显。结论:ZX-5和(R,R)-ZX-5对增加脉络膜血流量和促进视网膜功能的恢复有显著功效,(R,R)-ZX-5恢复视网膜功能的作用更强,有可能进一步开发成有效防治眼血流障碍相关性眼病的药物。     

In vivo measurement of ocular circulation with the laser speckle method--development of apparatus and application in ophthalmological research

We have developed an apparatus utilizing laser speckle phenomenon which can measure the peripheral circulation in the iris, choroid, retina and optic nerve head (ONH) and blood velocity through retinal vessels in the living eye non-invasively and quantitatively. A blue-component argon laser (wavelength 488 nm) was used for measurement of peripheral circulation in the retina and a diode laser (wavelength 808 nm) for measurements of peripheral circulation in the iris, posterior choroid and ONH, and measurement of centerline blood velocity through retinal vessels. A fundus camera (TRC-WT 3, Topcon) was equipped with a laser source and an image sensor where the speckle pattern from the fundus appears, and the data were analyzed with a personal computer to give a normalized blur (NB) value or a square blur rate (SBR) value, both quantitative indices of blood velocity. The NB value, whose computation requires much less time, was adopted to evaluate peripheral circulation because of non-linear correlation between the NB and actual blood velocity in the range above 20 mm/sec. The SBR value, whose computation requires a longer time, was adopted for measurement of blood velocity through retinal vessels. Measurement field in the living eye was 1.06 x 1.06 mm at its maximum and reproducibility index of the in vivo measurement in the rabbit iris, choroid, retina, and ONH was approximately 10%. When blood flow was changed by intraocular pressure (IOP) change in rabbit eyes, NB values obtained from the iris, choroid, and retina showed a significant correlation with the blood flow simultaneously determined with the colored microsphere technique in the same eye, and the NB obtained from the ONH also correlated with the blood flow determined with the H2 gas clearance method. Stepwise reduction in the ocular perfusion pressure (OPP) by stepwise increment of IOP resulted in proportional reduction in the iris- and choroid-NB. On the other hand, the retina- or ONH-NB remained almost unaltered at OPP levels above 50 mmHg, and decreased along with OPP at levels less than 50 mmHg. By monitoring NB values for 2 hours, presence or absence of autoregulatory mechanism against OPP change in the choroidal and ONH circulation was studied in rabbits. Throughout the experimental period of 2 hours, the choroidal NB was changed along with the OPP change, suggesting absence of blood flow autoregulation in this tissue. In the ONH, however, the NB returned to the baseline after its transient increase or decrease when the OPP was continuously increased or decreased, showing the presence of an autoregulatory mechanism in the ONH circulation. However, the time course of the NB resumption depended on the extent of OPP change. These results indicated that the laser speckle method can be useful in investigating the autoregulatory mechanism and processes of peripheral circulation in ocular tissues. Unilateral instillation of drugs with vasodilative activity (ifenprodil, betaxolol or nipradilol) in rabbit eyes significantly increased ONH and/or choroidal circulation. The extent in change in the ONH and/or choroidal circulation correlated with the number of doses, but not with the extent of IOP reduction, which suggested that the observed effects were attributable to the drug which penetrated locally. Intravenous administration of a Ca(2+)-antagonist (nicardipine, nilvadipine or pranidipine) significantly increased choroidal or retinal circulation in rabbits. The ONH circulation, however, was not affected by nicardipine, but affected by nilvadipine or pranidipine. Given the same effect on the ONH circulation, systemic hypotensive effect was stronger in pranidipine than in nilvadipine, which suggested that nilvadipine can be used in patients with ocular circulatory insufficiency. A modification of the laser speckle apparatus used for animal experiments was devised so that the NB or SBR values could be measured in human eyes every 0.12 sec on a real-time basis. (ABSTRACT TRUN     

Laser Doppler flowmetry and optic nerve head blood flow

PURPOSE: Ischemic disorders of the optic nerve head constitute an important cause of visual loss. The optic nerve head is supplied by two main sources of blood flow: the superficial layers by the central retinal artery and the deeper layers by the posterior ciliary arteries. This study was conducted in rhesus monkey eyes to obtain a better understanding of which part of the optic nerve head circulation is measured by laser Doppler flowmetry. METHODS: By means of a fundus camera-based laser Doppler flowmetry technique to measure blood flow in the optic nerve head tissue, laser Doppler flowmetry measurements were taken at baseline and then after experimental occlusion of central retinal artery (12 eyes), posterior ciliary arteries (nine eyes), and combined occlusion of central retinal artery and posterior ciliary arteries (nine eyes). Optic nerve head, choroidal, and retinal circulations were investigated by fluorescein fundus angiography after the various arterial occlusions. RESULTS: Average laser Doppler flowmetry flow during central retinal artery occlusion alone was significantly decreased (P<.001) by 39%+/-21% (mean +/- 95% confidence interval) compared with normal baseline. Combined occlusion of central retinal artery and posterior ciliary arteries reduced laser Doppler flowmetry flow even more markedly by 57%+/-27% (P<.0005), but the difference between this flow reduction and that with central retinal artery occlusion alone was not significant (P>.20). After posterior ciliary artery occlusion alone, however, measurements showed a nonsignificant increase in laser Doppler flowmetry flow of 17%+/-37%. CONCLUSIONS: The findings of this study suggest that the standard laser Doppler flowmetry technique is predominantly sensitive to blood flow changes in the superficial layers of the optic nerve head and less sensitive to those in the prelaminar and deeper regions, and their relative proportions are not known. In this laser Doppler flowmetry technique, the weaker Doppler signal from the deep layers cannot be separated from the dominant signal from the superficial layers to exclusively study the circulation in the deep layers; the latter circulation is of interest in optic nerve head ischemic disorders, including glaucoma. Emerging new optical modalities of the laser Doppler flowmetry technique may help in selectively measuring blood flow in the deeper layers.     

Latanoprost及Unoprostone对兔及猴葡萄膜MMP-2表达影响的研究

目的：研究PGF2α类抗青光眼药Latanoprost和Unoprostone对兔及猴的降眼压途径有否不同。方法：1．用0．005Latanoprost、0．12％Unoprostone分别对12只兔、8只猴发10天,测量点眼前后兔及猴眼压,兔眼前房水蛋白浓度。2．采用Zymography技术对兔、猴点眼后葡萄膜中MMP－2活性进行定量分析。结果：①Latanoprost及Unoprostone都可有效降低兔及猴眼压,并且对兔眼前房水蛋白浓度无明显影响。②两种药物点眼后,猴葡萄膜中MMP－2活性增强,却对兔葡萄膜中MMP－2活性均无明显影响。结论：Latanoprost及Unoprostone对猴的降眼压作用机制在于影响了葡萄膜巩膜房水流出,而对兔眼的降压效果可能存在其他途径。     

Changes in optic nerve head blood flow after therapeutic intraocular pressure reduction in glaucoma patients and ocular hypertensives

PURPOSE: To detect and quantify changes in optic nerve head (ONH) and peripapillary retinal blood flow by scanning laser Doppler flowmetry (SLDF) in open-angle glaucoma (OAG) and ocular hypertension (OHT) after therapeutic intraocular pressure (IOP) reduction. DESIGN: Prospective, nonrandomized, self-controlled trial. PARTICIPANTS: Twenty patients with OAG and 20 patients with OHT with clinical indications for therapeutic IOP reduction were prospectively enrolled. INTERVENTION: IOP reduction was achieved by medical, laser, or surgical therapy. All patients had IOP reductions more than 20% and a minimum of 4 weeks follow-up. MAIN OUTCOME MEASURES: Blood flow measurements were performed by SLDF analysis software (version 3.3) using Heidelberg Retina Flowmeter images. Statistical evaluations were performed on both groups using a two-tailed distribution paired t test. RESULTS: Twenty patients with OAG had a mean IOP reduction of 37% after treatment. In these patients, mean (+/- standard deviation) rim blood flow increased by 67% (from 158 +/- 79 arbitrary units to 264 +/- 127 arbitrary units, P = 0.001), whereas mean temporal peripapillary retinal flow decreased by 7.4% (P = 0.24), and mean nasal peripapillary retinal flow increased by 0.3% (P = 0.96). Twenty OHT patients had a mean IOP reduction of 33% after treatment. In contrast to the OAG group, neither the mean rim blood flow (7.5% increase from 277 +/- 158 arbitrary units to 298 +/- 140 arbitrary units, P = 0.41) nor the mean temporal (P = 0.35) or nasal (P = 0.88) peripapillary retinal flow changed significantly. CONCLUSIONS: For a similar percentage of IOP reduction, OAG patients had a statistically significant improvement of blood flow in the neuroretinal rim of the ONH, whereas OHT patients did not demonstrate such a change. Peripapillary retinal blood flow, expected to be affected less in glaucoma, remained stable in both groups. In addition to indicating a response to therapy in OAG patients, the reported changes in rim perfusion suggest that ONH autoregulation may be defective in OAG while intact in OHT.     

Retinal temperature increase during transpupillary thermotherapy: effects of pigmentation, subretinal blood, and choroidal blood flow

PURPOSE: To study the risk of adverse events in transpupillary thermotherapy (TTT) for age-related macular degeneration by measuring how laser-induced retinal temperature increase is affected experimentally by subretinal blood, choroidal blood flow, and chorioretinal pigmentation. METHODS: An ultrafine thermocouple technique was developed to measure retinal temperature increase during TTT in albino and pigmented rabbit eyes. TTT was performed with 60-second, 0.78-mm spot size, 810-nm infrared diode laser exposures with power settings ranging from 50 to 950 mW. Intraretinal and subretinal temperature increases were measured in pigmented and albino rabbits, with or without subretinal blood and choroidal blood flow. RESULTS: Threshold power settings for visible lesions in albino and pigmented rabbits were 950 and 90 mW, respectively, corresponding to retinal temperature increases of 11.8 degrees C and 5.28 degrees C, respectively. Power settings required to produce threshold lesions in albino rabbits caused retinal temperature increases in pigmented rabbits that were five times higher than in the albino rabbits. Temperature increases in albino rabbits were 1.5 times higher with subretinal blood than without it. Choroidal blood flow generally did not affect measured retinal temperature increases. CONCLUSIONS: The results confirm prior theoretical recommendations that clinicians should consider decreasing TTT power settings in darkly pigmented eyes and proceed with caution in those with subretinal hemorrhage or pigment clumping.     

Two dimensional mapping of the perfusion of the retina and optic nerve head.

AIM--To present a new non-invasive method of performing a high definition topography of perfused vessels of the retina and the optic nerve head with simultaneous evaluation of blood flow. METHOD--By a combination of a laser Doppler flowmeter with a scanning laser system the perfusion of the retina and the optic nerve head is visualised. The principles of measuring blood flow by laser Doppler flowmetry are based on the optical Doppler effect: laser light scattered by a moving particle is shifted in frequency by an amount delta f. Our data acquisition and evaluation system is a modified laser scanning tomograph. The technical data are retinal area of measurement 2.7 mm x 0.7 mm, 10 degrees field with 256 points x 64 lines, measurement accuracy 10 microns, wavelength 670 nm and 790 nm, light power 100 microW and 200 microW, data acquisition time 2.048 s. Every line is scanned 128 times by a line sampling rate of 4000 Hz. By performing a discrete fast Fourier transformation over 128 intensities of each retinal point the laser Doppler shift is calculated for each retinal point. With these data a two dimensional map with 256 x 64 points of the retinal perfusion is created. The brightness of the pixel is coded by the value of the Doppler shift. Offline capillary blood flow is estimated in arbitrary units according to the theory of laser Doppler flowmetry in every region of interest of the perfusion picture. We estimated the reliability and the validity of the method. Retinal blood flow was measured by scanning laser Doppler flowmetry (SLDF) while varying intraocular pressure by a suction cup of three healthy volunteers. Measurements of retinal blood flow performed in 47 eyes by the presented method (SLDF) were correlated with data gained by a commercially available laser Doppler flowmeter. Perfusion pictures of the superficial retinal layer and of deep prelaminar layers in the optic nerve head are presented. RESULTS--The reliability coefficients r1 of 'flow', 'volume', and 'velocity' were 0.84, 0.85, and 0.84 respectively. We found a significant linear relation between SLDF flow and the ocular perfusion pressure (r = 0.84, p < 0.001). Comparative measurements of the retinal blood flow by SLDF and a commercially available laser Doppler flowmeter showed a linear and significant relation (flow r = 0.6, p < 0.0001, volume r = 0.4, p < 0.01). Capillaries of the retinal superficial vasculature or deep ciliary sourced capillaries of the optic nerve head became visible with a high resolution by the confocal technique dependent on the focus. Offline, the blood flow variables of areas of 100 microns x 100 microns were calculated. CONCLUSION--SLDF enables the visualisation of perfused capillaries and vessels of the retina and the optic nerve head in high resolution by two dimensional mapping of perfusion variables which are encoded by the Doppler signal. This method achieves simultaneously qualitative and quantitative evaluation of capillary blood flow of distinct areas of the capillary meshwork.     

Evaluation of optic nerve head and peripapillary retinal blood flow in glaucoma patients, ocular hypertensives, and normal subjects

PURPOSE: To compare optic nerve head (ONH) and peripapillary retinal blood flow in subjects with open-angle glaucoma (OAG), ocular hypertension (OHT), and normal eyes (NOR) using full-field perfusion analysis of scanning laser Doppler flowmetry (SLDF) images. DESIGN: Prospective, nonrandomized clinical trial. METHODS: Twenty uncontrolled OAG patients, 20 uncontrolled OHT patients, and 20 normal volunteers were prospectively enrolled. Mean ONH and peripapillary retinal blood flow measurements were performed by SLDF version 3.3 using five Heidelberg Retina Flowmeter (Heidelberg Engineering, Heidelberg, Germany) images. Statistical evaluations were performed on the three study groups using one-way analysis of variance. Flow values of the neuroretinal rim of the ONH, nasal peripapillary retina, and temporal peripapillary retina were then correlated with the clinical parameters of age, cup/disk (C/D) ratio, intraocular pressure (IOP), visual field mean defect, maximum-recorded IOP, and ocular perfusion pressure.Neuroretinal rim blood flow in the OAG group was 158 +/- 79 arbitrary units (au), whereas in the OHT group it was 277 +/- 158 au, and in the NOR group it was 272 +/- 93 au. Differences were statistically significant between the OAG group and each of the other groups (P =.001) but not between OHT and NOR groups (P =.91). Peripapillary retinal flow values showed no statistically significant differences between groups (P =.76 nasal and 0.93 temporal). RESULTS: Neuroretinal rim flow values showed a significant inverse correlation with C/D ratio (P =.001). Mean neuroretinal rim blood flow was significantly higher (350 +/- 184 au) in the 10 OHT patients with C/D ratios < 0.4 when compared with the 10 OHT patients with larger C/D ratios (203 +/- 79 au) (P =.039). Conversely, peripapillary retinal blood flow showed no significant correlation with any clinical parameter. CONCLUSION: Open-angle glaucoma patients had significantly lower blood flow in the ONH compared with OHT patients and normal volunteers. No significant differences in ONH blood flow were found between ocular hypertensives and normal volunteers. For peripapillary retinal blood flow, no significant difference was seen between any groups. Neuroretinal rim blood flow was significantly inversely correlated to increased C/D ratio. Ocular hypertensives with larger C/D ratios demonstrated significantly lower rim blood flow compared with those with smaller C/D ratios, suggesting that rim perfusion might be reduced in high-risk ocular hypertensives before the manifestation of visual field defects.     

Vascular concepts in glaucoma

A relationship has been found among vascular risk factors, normal-tension glaucoma (NTG), and visual field progression. All these factors have been measured qualitatively. These factors are disc hemorrhages, peripapillary atrophy, myopic disc, choroidal sclerosis, slow filling of the choroid and veins, and vasospasms. Now we are in a transition period where more and more quantitative methods are becoming available: pulsatile ocular blood flow measurement (POBF), scanning laser angiography of the peripapillary choroid (SLAPPC), scanning laser angiography of the retinal circulation (SLARC), scanning laser Doppler flowmetry (SLDF), and color Doppler imaging. With POBF, SLAPPC, SLARC, and SLDF a deficient blood flow was found in at least 50% of patients with NTG. With these results a vascular pathogenesis of NTG becomes more and more evident.     

A rabbit model to study orbital venous pressure,intraocular pressure,and ocular hemodynamics simultaneously

PURPOSE: To measure orbital venous pressure (OVP) and determine the effects of changes in mean arterial pressure (MAP) on OVP, intraocular pressure (IOP), episcleral venous pressure (EVP), and ciliary and choroidal blood flows. METHODS: The experiments were performed in anesthetized rabbits. In all animals, MAP, IOP, and OVP were measured by direct cannulation of the central ear artery, the vitreous, and the orbital venous sinus, respectively. Laser Doppler flowmetry was used to measure choroidal blood flow in one group, and ciliary blood flow in a second group. A servonull micropressure system was used to measure EVP in a third group. The protocol for all three groups entailed varying MAP mechanically with occluders on the aorta and vena cava. RESULTS: The OVP and IOP relationship correlated linearly (r = 0.99) during mechanical manipulation of MAP. EVP also correlated well with OVP (r = 0.9). Resistance calculations based on choroidal and ciliary blood flows and the pressure gradients indicate active adjustment of arterial resistance and passive changes in venous resistance in response to changing MAP in both circulations. CONCLUSIONS: The rabbit orbital venous sinus permits continuous measurements of OVP. The present findings show that OVP is not static and suggest that OVP may play an important role in IOP homeostasis and ocular hemodynamics.     

Autoregulation of choroidal blood flow in the rabbit.

Previous studies show that choroidal blood flow is not autoregulated when intraocular pressure (IOP) is increased to raise venous pressure and lower the perfusion pressure gradient. However, the autoregulatory response to changes in mean arterial pressure (MAP) is unclear. In the current study, the perfusion pressure gradient (MAP-IOP) was altered by (1) decreasing MAP while IOP was held at 5, 15, and 25 mmHg, and (2) increasing the IOP at the prevailing MAP in anesthetized rabbits (n = 8). An occluder on the thoracic vena cava was used to vary MAP; this was monitored through an ear artery catheter. Two catheters were inserted in the vitreous to monitor and control IOP. Choroidal blood flow was measured by laser Doppler flowmetry using a slender stainless-steel probe positioned next to the retinal surface. The efficacy of autoregulation depended on the IOP. When IOP was held constant at 5 mmHg, choroidal blood flow did not fall until the perfusion pressure gradient was less than 40 mmHg. The pressure-flow relationship became progressively more linear (ie, the efficacy of autoregulation decreased) when the IOP was held constant at 15 and 25 mmHg. When IOP was varied and MAP was held constant, the pressure-flow relationship was linear at IOPs greater than 20-25 mmHg. However, choroidal blood flow was pressure independent when the IOP was less than 20-25 mmHg. Simultations using a myogenic mathematic model of the choroid gave results similar to the experimental observations. It was concluded that a myogenic mechanism may be responsible for the autoregulation of choroidal blood flow in the rabbit.     

The influence of ocular pulsatility on scanning laser Doppler flowmetry.

PURPOSE: To determine the effect of the cardiac cycle on scanning laser Doppler flowmeter measurements of retinal capillary blood flow in rhesus monkeys and humans. METHODS: Multiple scanning laser Doppler flowmetry images of rhesus monkey and human retinal capillary blood flow over a range of heart rates were obtained. Average flow values were determined for the 64 scan lines that compose the two-dimensional flow map. Cutaneous blood flow was measured simultaneously with a laser Doppler flowmeter. The temporal relationships between retinal capillary blood flow, peripheral arterial pulse, and cutaneous blood flow were determined. In addition, human retinal capillary blood flow in a 10 x 10-pixel area during different phases of the cardiac cycle was compared. RESULTS: Regular oscillations in human and rhesus monkey retinal capillary blood flow are evident as alternating bright and dark horizontal bands in scanning laser Doppler flowmetry images. These fluctuations are temporally correlated with cutaneous blood flow. Linear regression of actual vs predicted heart rate based on peaks in retinal capillary flow yielded r = 0.999 in a rhesus monkey and 0.938 in a human. Retinal capillary blood flow in a 10 x 10-pixel area fluctuated as much as 50% depending on the phase of the cardiac cycle. CONCLUSIONS: The alternating bright and dark banding pattern observed in scanning laser Doppler flowmetry scans of retinal capillary blood flow is related to the cardiac pulse. The errors introduced by pulse-related fluctuations in retinal capillary blood flow are significant and must be minimized or corrected for accurate and reproducible measurements of ocular hemodynamics.     

大麻素(WIN55,212-2)对高眼压家兔模型降眼压作用的研究

目的 评价大麻素(WIN55,212-2)滴眼液在卡波姆诱导的兔慢性高眼压模型中的降压作用.方法 人工诱导兔慢性高眼压模型.取右眼高眼压兔24只,随机分为A、B、C 3个组,每组8只.右眼结膜囊内分别滴入0.125%大麻素滴眼液、0.5%噻吗心胺滴眼液及生理盐水,用药后每日测眼压1次.任选8只左眼为D组作空白对照.结果 用药1周后眼压大麻素组为用药前的69%,噻吗心胺组为78%;用药3周后眼压大麻素组为用药前的45%,噻吗心胺组为60%.各组间最大降眼压幅度差异有统计学意义(P＜0.01).结论 0.125%大麻素滴眼液点眼降眼压作用确定,与0.5%噻吗心胺比较,持续时间长,下降幅度大.     

Short-term effect of beta-adrenoreceptor blocking agents on ocular blood flow

PURPOSE: In this study the acute effect of the topically-delivered non-selective beta-blockers timolol and carteolol, and the selective beta-blocker betaxolol, were evaluated with respect to ocular blood flow, intraocular pressure (IOP) and vessel resistance in rabbits' eyes. METHODS: In a double masked randomized design, one eye of each subject (n = 9) received two drops of 0.5 % timolol or 2 % cartelol or 0.5 % betaxolol ophthalmic solution and a separate group of nine rabbits received two drops of placebo consisting of physiological saline in both eyes to serve as control. Using hydrogen clearance method, ciliary body blood flow (CiBF), choroidal blood flow (CBF), and retinal blood flow (RBF) were measured. IOP and systemic mean arterial pressure (MAP) of each subject were measured under same condition before and after the administration of respective drugs to calculate the ocular perfusion pressure (OPP) and vessel resistance. RESULTS: In timolol- and carteolol-treated eyes significant reduction was observed in IOP (p < 0.01), CiBF (p < 0.01), CBF (p < 0.01) and RBF (p < 0.01) compared to control eyes. However, in betaxolol-treated eyes a marginal reduction in IOP was observed accompanied by significant increase in CiBF (p < 0.01) and RBF (p < 0.05). The non-selective beta-blocker-treated eyes tended to have increased vessel resistance, whereas, selective beta-blocker-treated eyes tended to have decreased vessel resistance. CONCLUSIONS: Our current results comparing non-selective and selective beta-blockers suggest that the selective beta-blocker betaxolol may be more appropriate for maintenance of retinal blood flow in situations with low perfusion. Currently the mechanism for regulation of IOP is unclear; however, the findings from this study indicate that decreased CiBF may contribute to reduction in IOP.     

Endothelin-1-mediated retinal artery vasospasm and the rabbit electroretinogram.

Electroretinogram (ERG) changes invariably accompany the selective interruption of the retinal circulation that occurs in human central retinal artery occlusion. Since arteriolar ligation or ocular hypertension in the rabbit eye is occasionally used to model human central retinal artery occlusion, we conducted the present study to determine whether selective interruption of the retinal circulation of the rabbit eye alters retinal function as measured by the ERG. The vasoconstrictor, endothelin-1, was injected into the vitreous of rabbits' eyes to induce complete vasospasm and selective interruption of the retinal circulation. This procedure was compared to vascular ligation of the ophthalmic and ciliary arteries in which both the retinal and choroidal circulations were interrupted. A total of 8 rabbits was studied. Circulation was monitored angiographically in half of the eyes, and retinal function was monitored by the ERG in the remaining eyes. Endothelin-1 obliterated retinal arteriolar blood flow without affecting choroidal blood flow for at least 1 hr. Although ERG a-wave amplitude showed a small decline over 2 hr, b-wave and oscillatory potential amplitudes (measures of inner retinal function) showed no loss over this period. In contrast, ligation of the ophthalmic and ciliary arteries produced complete obliteration of both retinal arteriolar and choroidal blood flow and complete loss of the ERG after 2 min. Endothelin-1 induces acute, selective interruption of retinal arteriolar blood flow which has no significant physiologic effect on inner retinal function of the rabbit as monitored by the ERG. The avascular rabbit retina appears to be a poor choice for modeling human retinal artery occlusion.     

The effect of topical PGF2 alpha on uveoscleral outflow and outflow facility in the rabbit eye.

Prostaglandin F2 alpha (PGF2 alpha) is a powerful ocular hypotensive agent in rabbit, cat, dog, monkey and human. In cynomolgus monkeys, the intraocular pressure (IOP) lowering is due to increased uveoscleral outflow (Fu). Because the anatomy of the rabbit outflow apparatus differs significantly from that of the primate, we sought to determine whether the mechanism of the PGF2 alpha-induced IOP fall was the same. PGF2 alpha tromethamine salt (PGF2 alpha-TS) (50 micrograms) applied to one eye of 14 conscious rabbits produced a significant IOP fall of 7.4 +/- 0.9 mmHg (P less than 0.001). In untreated control eyes, Fu determined from the quantity of intracamerally perfused [125I]albumin found in the ocular and periocular tissues accounted for 5-8% of total aqueous outflow. In 15 unilaterally PGF2 alpha-treated rabbits, after 4-6 hr dosing Fu was 49 +/- 14% higher in the treated than in the contralateral control eyes. Total outflow facility of outflow from the anterior chamber to the general circulation were measured concurrently in 11 rabbits using a two-level constant pressure perfusion and isotope accumulation technique. Both facilities tended to be higher in the treated eyes than in the controls, with a strong correlation between drug-induced changes in total facility and changes in facility of flow to blood (r = 0.85, P less than 0.001). In eight rabbits treated unilaterally with 50 micrograms PGF2 alpha-TS, the fluorophotometrically determined aqueous formation rate was probably not decreased relative to control eyes. Protein levels in the aqueous humor were approximately eight-fold higher in PG-treated vs. control eyes, suggesting a drug-induced compromise of the blood-aqueous barrier.(ABSTRACT TRUNCATED AT 250 WORDS)